1. Field of the Invention
The present invention relates to a modified sodium iodide symporter protein and its uses, and particularly relates to the uses of the modified sodium iodide symporter protein for increasing the substrates of the sodium iodide symporter protein within cells in vitro or in vivo.
2. Descriptions of the Related Art
The main function of thyroid hormones in the human body is to regulate physiological functions and promote metabolism. For example, thyroid hormones can regulate the oxygen consumption of cells, respiratory rate, body temperature, heartbeat, blood flow, etc., and also can promote the metabolism of fats, proteins, and carbohydrates. Iodine (I) is an essential element in thyroid hormones. Thyroid hormones are produced by the thyroid gland, and via a sodium iodide symporter (NIS) protein on the cell membrane of the thyroid gland, iodide ions (I−) in the blood are transferred to thyroid cells by active transport to synthesize thyroid hormones.
Thyroid cancer is a malignant neoplasm that commonly occurs in the region of the neck. Thyroid cancer has a long latency period with a fast transfer rate and has become one of the leading cancers for the female population in Taiwan over recent years. Radioactive iodine therapy is commonly used for the treatment of thyroid cancer. The specificity of the NIS protein transporting iodide ions is applied in this therapy to transfer a radioactive I-131 isotope into thyroid cancer cells to achieve the efficacy of killing cancer cells. Thus, in radioactive iodine therapy, the function of the NIS protein to transport iodide ions into the thyroid cancer patient has become a key factor in treatment. If the NIS protein cannot promptly transfer a sufficient concentration of radioactive iodide ions into thyroid cancer cells, then the cancer cells cannot be effectively killed to promote cancer therapy.
US Laid-Open Patent Application No. 2006/0004191 A1 discloses a modified NIS protein, of which the transport function for I− ions is enhanced by increasing the number of positive charges of the wild-type NIS proteins. Although this patent application mentions that a substitution method (i.e., neutral uncharged or negatively charged amino acids in the wild-type NIS protein are substituted by positively charged amino acids) or an addition method (i.e., positively charged amino acids are added to the wild-type NIS protein) can be used to modify the NIS protein and increase the amount of positive charged amino acids in the wild-type NIS protein, according to the examples disclosed therein, ten positively charged amino acids are added to the wild-type NIS protein to enhance its transport capability.
In fact, it is not that straightforward to simply replace the neutral uncharged or negatively charged amino acids with the positively charged amino acids within the NIS protein to achieve the improvement result as claimed in US 2006/0004191 A1. Furthermore, based on the teaching of US 2006/0004191 A1, if multiple positively charged amino acids are intentionally added to the wild-type NIS protein to increase the number of positively charged amino acids, then a sufficient amount of positively charged amino acids are required to achieve such an improved effect, thus increasing the cost of NIS protein production. As a result, an accurate and efficient modification method is still needed to increase the transport function of the NIS protein.
The research result of the present invention was carried out based on the above demand, and the inventors of the present invention found that the ability to transfer iodide ions of the NIS protein can be greatly enhanced by modifying a single or more amino acid residues within the NIS protein.